The primary goals of the proposed investigation are: 1. To determine the therapeutic and toxicological significance of the cardiac depressant effects of l-alpha acetylmethadol (LAAM). 2. To identify pharmacological and environmental factors that influence the disposition of (LAAM.) LAAM, an investigational drug, has been proposed as an alternative in the treatment of heroin addiction. Current work in this laboratory shows that the drug has direct negative inotropic and chronotropic effects in vitro. The dosage level at which such effects occur in vivo will be determined. Effects of LAAM on responses to cardioactive agents will be studied. The usefulness of LAAM in maintaining the tolerant state depends in large part upon metabolism of the drug to active forms. Factors that alter disposition of the drug must be identified. The effect of LAAM on the toxicity of other compounds of therapeutic or environmental importance must be determined. The latter studies will yield additional information on potential drug interactions. All of the information above must be obtained before LAAM is released for large scale use in the treatment of persons who have been identified as abusers of narcotics. Cardiovascular parameters (including blood pressure, and heart rate) will be monitored during and following chronic administration of LAAM. The effect of chronic administration of LAAM on the cardiovascular effects of other drugs also will be investigated. Physiological effects will be correlated with blood levels. The pattern of disposition for LAAM in normal male rats following acute administration will be compared with that in animals that are treated chronically with the drug. Disposition in pregnant dams and perinatal rats also will be observed. Effects of many pharmacological and toxicological interventions, including chronic morphine and methadone treatments, on LAAM disposition will be investigated. LAAM and metabolites will be identified by gas-liquid chromatography or a combination of gas-liquid chromatography and mass spectrometry.